Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators.

BACKGROUND: We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. METHODS AND RESULTS: One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) who had a pulmonary capillary wedge pressure >/=15 mm Hg and a cardiac index

Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. Studies of Left Ventricular Dysfunction.

OBJECTIVES: To assess the relation of left ventricular (LV) and left atrial (LA) dimensions, ejection fraction (EF) and LV mass to subsequent clinical outcome of patients with LV dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry and Trials. BACKGROUND: Data are lacking on the relation of LV mass to prognosis in patients with LV dysfunction and on the interaction of LV mass with other measurements of LV size and function as they relate to clinical outcome. METHODS: A cohort of 1,172 patients enrolled in the SOLVD Trials (n = 577) and Registry (n = 595) had baseline echocardiographic measurements and follow-up for 1 year. RESULTS: After adjusting for age, New York Heart Association (NYHA) functional class, Trial vs. Registry and ischemic etiology, a 1-SD difference in EF was inversely associated with an increased risk of death (risk ratio, 1.62; p = 0.0008) and cardiovascular (CV) hospitalization (risk ratio, 1.59; p = 0.0001). Consequently, the other echo parameters were adjusted for EF in addition to age, NYHA functional class, Trial vs. Registry and ischemic etiology. A 1-SD difference in LV mass was associated with increased risk of death (risk ratio of 1.3, p = 0.012) and CV hospitalization (risk ratio of 1.17, p = 0.018). Similar results were observed with the LA dimension (mortality risk ratio, 1.32; p < 0.02; CV hospitalizations risk ratio, 1.18; p < 0.04). Likewise, LV mass > or =298 g and LA dimension > or =4.17 cm were associated with increased risk of death and CV hospitalization. An end-systolic dimension >5.0 cm was associated with increased mortality only. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% had lower mortality) but not in the group with LV mass <298 g. CONCLUSIONS: In patients with LV dysfunction enrolled in the SOLVD Registry and Trials, increasing levels of hypertrophy are associated with adverse events. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% fared better) but not in the group with LV mass <298 g. These data support the development and use of drugs that can inhibit hypertrophy or alter its characteristics.

Ejection fraction response to supine exercise in asymptomatic aortic regurgitation: relation to simultaneous hemodynamic measurements.

The change in ejection fraction during exercise is frequently employed as a measure of left ventricular functional reserve in patients with aortic regurgitation. However, little information is available about its relation to invasive measurements of cardiac performance. Therefore, simultaneous hemodynamic measurements and supine exercise blood pool scintigraphy were performed in 14 patients with severe, asymptomatic or minimally symptomatic aortic regurgitation associated with cardiomegaly but preserved left ventricular function at rest. Their hemodynamic measurements at rest were normal and their exercise capacity was excellent. When the patients were categorized into those patients whose ejection fraction increased or did not decrease by more than 0.05 (Group 1) and those whose ejection fraction decreased by more than 0.05 (Group 2), important differences were apparent. Echocardiographic, radionuclide and hemodynamic measurements at rest in the two patient groups were similar, but Group 1 exhibited a greater increase in cardiac index during supine exercise (2.8 +/- 0.4 to 10.0 +/- 1.8 versus 2.7 +/- 0.5 to 6.9 +/- 1.0 liters/min per m2; p less than 0.005) and a lesser increase in pulmonary capillary wedge pressure (13 +/- 4 to 19 +/- 7 versus 12 +/- 4 to 31 +/- 8 mm Hg; p less than 0.01). The severity of regurgitation decreased during exercise in all patients, but end-diastolic volume decreased and end-systolic volume decreased or was unchanged in Group 1, whereas end-diastolic volume was unchanged and end-systolic volume increased in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Static exercise with congestive heart failure and the response to vasodilating drugs.

The hemodynamic response to static exercise in 28 patients with congestive heart failure (CHF) was compared with that in 8 control subjects. Static handgrip exercise at 50% of the maximal voluntary contraction was performed to fatigue. In patients with CHF, pulmonary arterial wedge pressure increased from 20 +/- 18 to 31 +/- 10 mm Hg (p less than 0.001) (mean +/- standard deviation) and systemic vascular resistance increased from 1,730 +/- 454 to 2,151 +/- 724 dynes s cm-5 (p less than 0.001). Although cardiac index did not change significantly, stroke volume index and stroke work index decreased from 24 +/- 6 to 20 +/- 6 ml/m2 (p less than 0.001) and 28 +/- 11 to 25 +/- 12 g-m/s2 (p less than 0.05), respectively. In control subjects, pulmonary arterial wedge pressure did not change significantly; cardiac index increased from 3.6 +/- 0.3 to 4.0 +/- 0.4 liters/min/m2 (p less than 0.05) and systemic vascular resistance increased slightly, from 1,011 +/- 186 to 1,106 +/- 180 dynes s cm-5 (p less than 0.05). The effects of arterial dilation with hydralazine on the response to static exercise were assessed in 10 of the patients with CHF. Compared with predrug exercise, cardiac index increased 68% (p less than 0.01), stroke volume index increased 76% (p less than 0.01) and systemic vascular resistance decreased 47% (p less than 0.01) after administration of hydralazine. Thus, static exercise can have adverse effects on cardiac performance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular response to submaximal and maximal exercise in asymptomatic aortic regurgitation.

In patients with chronic aortic regurgitation the quantitative changes in loading conditions and left ventricular performance from rest to submaximal exercise have not been related to the magnitude of change observed from rest to maximal exercise. Changes in end-diastolic volume index, as a measure of preload, and measures of contractile performance (ejection fraction and the systolic blood pressure/end-systolic volume index ratio) were assessed at rest, submaximal and maximal supine bicycle exercise using radionuclide angiography in 74 patients with chronic moderate to severe aortic regurgitation. With exercise, end-diastolic volume index decreased in a stepwise manner from 166 +/- 47 to 152 +/- 41 to 143 +/- 41 ml/m2 at rest, submaximal and maximal exercise, respectively. For the entire group, these changes were not associated with a significant change in ejection fraction but were associated with stepwise increases in systolic blood pressure to end-systolic volume index ratio. However, when patients were divided into 3 subgroups based on an increase (group I), minimal change (group II) or a decrease (group III) in ejection fraction from rest to maximal exercise, stepwise increases in systolic blood pressure to end-systolic volume index were again observed in groups I and II but not in group III. These changes were significantly greater in group I than in group II at submaximal and maximal exercise levels. Differences in ejection fraction response and end-diastolic and end-systolic volumes with exercise in the 3 groups were evident at the submaximal exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium-201 myocardial perfusion scintigraphy to evaluate patients after coronary bypass surgery.

To determine the utility of thallium-201 stress scintigraphy in assessing the results of coronary bypass surgery, chest pain, stress electrocardiograms and scintigrams were evaluated in 27 patients postoperatively. These findings were compared with coronary angiographic data in which a significant postoperative lesion was defined as 75 percent or more stenosis in a graft, its distal vessel or in an ungrafted native vessel. As an indicator of postoperative coronary lesions, chest pain lacked sensitivity (60 percent) and was nonspecific (20 percent). The stress electrocardiogram had poor sensitivity (60 percent) and good specificity (86 percent) but was not helpful in six patients who had equivocal or suboptimal tests. The scintigram had good sensitivity (77 percent) and was highly specific for the diagnosis of coronary stenosis. It was significantly more specific than chest pain (P less than 0.01), gave excellent localizing information and added to the accuracy of both conclusive and inconclusive stress tests. In nine patients with preoperative stress scintigrams, comparison of pre- and postoperative studies reflected the éffects of bypass surgery on coronary perfusion. Scintigraphy is a useful technique for the noninvasive evaluation of the patient after coronary bypass surgery, and postoperative scintigraphy alone is of great value in documenting surgical results.

The preoperative evaluation in patients with endocarditis. Is cardiac catheterization necessary?

We retrospectively compared clinical assessment and cardiac catheterization to subsequent surgical findings with regard to specific valvular involvement, hemodynamic status, and presence of myocardial abscess in patients recommended for cardiac surgery for endocarditis. Of 105 consecutive patients with endocarditis, 19 met one or more of the following criteria suggesting the need for early surgery: congestive heart failure; systemic emboli; persistent infections or new conduction abnormalities. Of these 19 patients, seven had prosthetic cardiac valves. Clinical assessment was highly sensitive (95 percent) and specific (89 percent) for specific valvular involvement and was also highly sensitive and specific in evaluating myocardial abscess and congestive heart failure; however, clinical assessment could not identify the source of infection in one patient with multiple prosthetic valves, did not define the specific valve in one patient with right-sided endocarditis, and overestimated the severity of mitral regurgitation in one patient who had normal pressures and flows at catheterization. Catheterization incorrectly predicted multivalvular involvement in four patients. At catheterization, only one patient experienced evidence of clinical deterioration, and this was probably not related to the procedure. We conclude that although clinical assessment is correct in most patients, it may on occasion lead to an erroneous conclusion. Catheterization and angiograms are of value in the preoperative evaluation of patients with endocarditis, particularly in cases where the clinical assessment is ambiguous or uncertain. The procedures can be performed at low risk, and the information obtained may substantially influence management in some cases.

Does the magnitude of mitral regurgitation determine hemodynamic response to vasodilation in chronic congestive heart failure?

Although it is usually assumed that direct-acting vasodilators improve cardiac function in patients with congestive heart failure (CHF) by altering left ventricular preload and afterload, several studies have suggested that most of the benefit occurs as a result of a reduction in associated mitral regurgitation (MR), which is present in the majority of patients with severe CHF. To test his hypothesis, the hemodynamic response to oral hydralazine was examined in CHF patients with competent mitral prostheses (group 1) and patients with CHF due to severe MR and left ventricular dysfunction (group 2). Both groups demonstrated significant increases in cardiac, stroke volume, and stroke work indices, although these were greater in group 2. Only group 2 experienced a significant reduction in left ventricular filling pressure. Thus, the presence of MR is not essential for hemodynamic improvement but is associated with significantly greater responses.

The relationship between functional class and cardiac performance in patients with chronic aortic insufficiency.

We have evaluated the relationship of New York Heart Association functional class (FC) assessment to rest and exercise hemodynamics and resting left ventricular (LV) functional data in 75 consecutive patients with isolated, chronic aortic insufficiency. Although there was a tendency for hemodynamic and angiographic variables to worsen as FC increased there was considerable overlap between patients assigned to the various groups. Statistically significant differences were seen only for resting left ventricular end-diastolic pressure (LVEDP) and pulmonary artery wedge (PAW) pressure which were higher in FC 3/4 patients than in FC 1 or 2 patients. The results of our study suggest that FC assignment cannot be used to accurately define underlying LV performance or hemodynamics in an individual patient with chronic aortic insufficiency. However, since severe abnormalities are unlikely to be present in asymptomatic patients, routine detailed frequent investigation does not seem warranted in this group. As FC worsens, the likelihood of left ventricular dysfunction increases. Thus, the presence of symptoms is an indication for more extensive evaluation.

Medical therapy for patients with aortic insufficiency.

The medical course and management of patients with aortic insufficiency depends on the severity of the valve lesion and acuity with which it develops. In this article a description of the basic pathophysiology of aortic insufficiency and the natural history of the disease is outlined. Recent information describing both the acute and long-term effects of vasodilator therapy is summarized. With this information, a rational approach to the medical management of aortic insufficiency is developed.

Evaluation of left ventricular performance by gated radionuclide angiography.

Gated radionuclide angiography (RVG) in orthogonal projections was used to evaluate left ventricular volume, ejection fraction, and segmental wall motion. Images of the left ventricle at end-diastole and end-systole were outlined in two projections using a simple manual method. The perimeter drawings were digitized on a desktop computer, interfaced to an XY recorder and left ventricular volumes and ejection fraction calculated. The results were compared to contrast left ventriculography (CVG) in the same projections. RVG and CVG gave similar results for end-diastolic volume (r = .87, P less than 0.001), end-systolic volume (r = .95, P less than 0.001), and ejection fraction (r = .89, P less than 0.001) over a wide range of values. In 92% of all left ventricular segments analyzed, RVG and CVG showed only minor differences in the analysis of wall motion. Reproducibility of the method by a trained observer was excellent. Interobserver trials demonstrated that less well-trained observers consistently over- or underestimated volumes, emphasizing the need for prior experience in RVG analysis. Use of this manual method for analysis of gated equilibrium RVG in orthogonal projections appears to be a reasonably accurate, reproducible method for evaluating left ventricular function.